Safety of pyrazinamide in elderly patients with TB in Japan

Who

• Participants: Hospitalized patients with tuberculosis (TB) in Japan

• Sample size:

  • 69,474 TB hospitalizations identified

  • 19,930 patients met inclusion criteria

  • 3,578 propensity score–matched pairs (7,156 patients)

• Age: Mean age ≈ 80 years after matching; subgroup analyses for ≥75 vs <75 years

• Key exclusions: Patients <15 years, pregnant patients, early deaths/discharges (≤2 days), and those not started on standard TB therapy promptly

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What

• Main finding: Adding pyrazinamide (PZA) to the initial TB regimen was not associated with increased in-hospital mortality in elderly patients.

• Adverse events:

  • Overall adverse events were more frequent with PZA-containing regimens, driven mainly by allergic reactions.

  • No significant differences in hepatotoxicity, gout attacks, gastrointestinal intolerance, length of hospital stay, or 90-day readmission.

• Conclusion: Advanced age alone should not be a reason to avoid PZA in TB treatment, though clinicians should monitor for allergic reactions.

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When

• Study period: July 2010 to March 2022

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Where

• Setting: Nationwide inpatient acute-care hospitals across Japan

• Context: Japanese policy mandates hospitalization for sputum smear–positive TB until smear conversion

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Why

• Rationale:

  • PZA is often avoided in elderly TB patients due to safety concerns.

  • Existing evidence was limited to small studies with poor generalizability.

  • This study aimed to provide robust, nationwide evidence on the safety of PZA in older adults with TB.

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How

• Design: Retrospective nationwide cohort study

• Data source: Japanese Diagnosis Procedure Combination inpatient database

• Exposure groups:

  • HRE (isoniazid, rifampicin, ethambutol)

  • HREZ (isoniazid, rifampicin, ethambutol, pyrazinamide)

• Analysis:

• Propensity score matching to balance baseline characteristics

• Primary outcomes: in-hospital mortality and composite adverse events

• Secondary outcomes: length of stay, readmission, and medication use for complications

• Sensitivity analyses stratified by age (≥75 vs <75 years)

Source: Taniguchi, J., Jo, T., Aso, S., Matsui, H., Fushimi, K. and Yasunaga, H., 2024. Safety of pyrazinamide in elderly patients with tuberculosis in Japan: A nationwide cohort study. Respirology, 29(10), pp.905-913.